ArticleNature communications2019
Biallelic mutations in valyl-tRNA synthetase gene VARS are associated with a progressive neurodevelopmental epileptic encephalopathy.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 34 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Genomic Biorepository: Protocol for the Collection, Storage, Analysis, and Distribution of Biological Samples, Genomic and Clinical Data
Rapid Whole Genome Sequencing (rWGS): Rapid Genomic Sequencing for Acutely Ill Patients and the Collection, Storage, Analysis, and Distribution of Biological Samples, Genomic and Clinical Data
Who cites it
34 citing papers in PubMed, 47 citations in OpenAlex.
- White matter disorders at the intersection of transcription, RNA processing and translation.Nature reviews. Neurology · 2026Review
- Novel VARS1 variants define new clinical and molecular subtypes of a rare neurodevelopmental syndrome.Biochimica et biophysica acta. Molecular basis of disease · 2026Article
- Integration of latent factor analysis into multivariable Mendelian randomization.European journal of epidemiology · 2026Article
- Lithium-induced neuroprotection in bipolar disorder: Translational insights into cytoskeletal and proteomic mechanisms.IBRO neuroscience reports · 2025Review
- Screening of metabolic markers in pediatric epilepsy disorders.Journal of translational medicine · 2025Article
- Setting the Stage for Treatment of Aminoacyl-tRNA Synthetase (ARS)1-Deficiencies: Phenotypic Characterization and a Review of Treatment Effects.Journal of inherited metabolic disease · 2025Review
- A Computational Recognition Analysis of Promising Prognostic Biomarkers in Breast, Colon and Lung Cancer Patients.International journal of molecular sciences · 2025Article
- Quantitative proteomic analysis unveils a critical role of VARS1 in hepatocellular carcinoma aggressiveness through the modulation of MAGI1 expression.Molecular cancer · 2025Article
- Aminoacyl-tRNA synthetase defects in neurological diseases.IUBMB life · 2025Review
- Simultaneous determination of cytosolic aminoacyl-tRNA synthetase activities by LC-MS/MS.Nucleic acids research · 2024Article
- Towards a Treatment for Leukodystrophy Using Cell-Based Interception and Precision Medicine.Biomolecules · 2024Review
- The 37TrillionCells initiative for improving global healthcare via cell-based interception and precision medicine: focus on neurodegenerative diseases.Molecular brain · 2024Review
- High expression of VARS promotes the growth of multiple myeloma cells by causing imbalance in valine metabolism.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023Article
- DNA Methylation Changes in Autologous Hematopoietic Stem Cell Transplant Patients.Biological research for nursing · 2023Article
- Targeted Sequencing Approach and Its Clinical Applications for the Molecular Diagnosis of Human Diseases.Cells · 2023Review
- Transcriptome-based network analysis related to M2-like tumor-associated macrophage infiltration identified VARS1 as a potential target for improving melanoma immunotherapy efficacy.Journal of translational medicine · 2022Article
- The tRNA regulome in neurodevelopmental and neuropsychiatric disease.Molecular psychiatry · 2022Review
- Emerging cellular themes in leukodystrophies.Frontiers in cell and developmental biology · 2022Review
- Hypertonia, Microcephaly and Hyperkalaemia in a Neonate: Coexistence of Neurodevelopmental Disorder and Adrenal Insufficiency.Iranian journal of child neurology · 2022Article
- Article
Corrections and comments
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Authors and funding
29 authors at 10 institutions in 7 countries.
Funding
Abstract
Aminoacyl-tRNA synthetases (ARSs) function to transfer amino acids to cognate tRNA molecules, which are required for protein translation. To date, biallelic mutations in 31 ARS genes are known to cause recessive, early-onset severe multi-organ diseases. VARS encodes the only known valine cytoplasmic-localized aminoacyl-tRNA synthetase. Here, we report seven patients from five unrelated families with five different biallelic missense variants in VARS. Subjects present with a range of global developmental delay, epileptic encephalopathy and primary or progressive microcephaly. Longitudinal assessment demonstrates progressive cortical atrophy and white matter volume loss. Variants map to the VARS tRNA binding domain and adjacent to the anticodon domain, and disrupt highly conserved residues. Patient primary cells show intact VARS protein but reduced enzymatic activity, suggesting partial loss of function. The implication of VARS in pediatric neurodegeneration broadens the spectrum of human diseases due to mutations in tRNA synthetase genes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.